Degradable Carrier-Free Metal-Phenolic Network Theranostic Agent with Targeted Mitochondrial Damage for Efficient Cancer Theranostics

Mitochondria-targeted cancer therapy holds great promise for anticancer treatments. It is thus of great significance to explore effective strategies for targeted mitochondrial damage in cancer cells. Herein, a degradable carrier-free curcumin-based metal-phenolic network (MPN) theranostic agent, namely, the indocyanine green-loaded curcumin-Gd nanoparticle (ICG@cur-Gd NP), is reported for magnetic resonance (MR)/fluorescence dual-modal imaging-guided chemo-/photodynamic combination cancer therapy. The ICG@cur-Gd NPs are fabricated by coordination-driven self-assembly of curcumin and Gd3+, followed by ICG loading. This theranostic agent intrinsically enables the MR and fluorescence imaging for real-time tumor visualization and precise guidance during anticancer treatments. Tumor-acidity-responsive degradation of ICG@cur-Gd NPs induces tumor-specific release of curcumin, ICG, and Gd3+ with no long-term systemic toxicity. The results reveal that the curcumin component of ICG@cur-Gd NPs can induce efficient mitochondrial damage. The excellent anticancer efficacy of ICG@cur-Gd NPs with laser exposure is confirmed in vivo, highlighting its potential for clinical use. This study constitutes the first report of a curcumin-based MPN theranostic agent combined with the clinically approved and used MR imaging contrast agent Gd3+. This work provides a novel and efficient strategy to construct carrier-free theranostic agents for imaging-guided cancer theranostics.